The invention relates to antimicrobial compositions for providing disinfecting treatment and sustained antimicrobial effectiveness to the skin surface with minimized skin irritation. In particular, the invention relates to compositions containing parachlorometaxylenol (PCMX) which are useful in surgical scrub and pre-operative skin disinfecting formulations.
Standard surgical procedures require disinfection of skin surfaces of both the surgeon and patient at the surgical site prior to surgery. Effective pre-operative cleansing of skin is critical to reducing the risk of infection to the patient. Surgical scrub and pre-operative skin preparations are therefore important to control the risk of infection.
Microorganisms on the skin can be transient or resident. Transient microorganisms lie on the surface of the skin, whereas resident microorganisms are found at deeper sites in the skin. It is desirable to kill microorganisms on the skin prior to surgery and sustain the antimicrobial activity of the skin surface as effectively as possible through the duration of the surgical procedure.
Effective antiseptic compositions can be produced by combining a surfactant or detergent with an antimicrobial agent. However, many such compositions are unsuitable for contact with human skin, and can cause discomfort and irritation to the skin. The development of formulations containing antimicrobial agents and detergents that provide acceptable antiseptic properties as well as avoid skin irritation has proven difficult, since the effectiveness of the antimicrobial agent is often reduced by the additional ingredients used.
Parachlorometaxylenol (PCMX) has a phenolic chemical structure and is related to compounds such as cresol, carbolic acid, and hexachloroprene. PCMX is a desirable antimicrobial agent and is particularly effective against a wide variety of gram-positive and gram-negative bacteria. PCMX goes by a variety of other names, including chloroxylenol; 4-chloro-3,5 xylenol; 4-chloro-3,5-dimethylphenol; 2-chloro-m-xylenol; 2-chloro-5-hydroxy-m-xylene; 2-chloro-5-hydroxy-m-xylene; 2-chloro-5-hydroxy-1,3-dimethylbenzene; 4-chlor-1-hydroxy-3,5-dimethyl benzene; and 3,5-dimethyl-4-chlorophenol. Antimicrobial formulations containing PCMX as a disinfecting ingredient are well-known in the art and disclosed by Garabedian et al., U.S. Pat. No. 4,632,772; Corti et al., U.S. Pat. No. 5,114,978; Kahn et al., U.S. Pat. No. 5,439,681; and Woodin, Jr. et al., U.S. Pat. No. 5,494,533.
The antimicrobial effectiveness of PCMX is desirable, however, formulations containing PCMX are difficult to prepare due to its incompatibility with many surfactants as well as other types of compounds. The efficacy of PCMX is often compromised by a variety of factors, such as additional ingredients (e.g., surfactants), pH level, and solubility. For example, see Kahn et al., U.S. Pat. No. 5,439,681, which discloses the difficulty of combining surfactants with PCMX while preserving antiseptic efficacy. Dryness and irritation to the skin are also frequently associated with phenolic antimicrobial compounds such as PCMX.
Development of an antimicrobial formulation containing PCMX which demonstrates both a high degree of antimicrobial effectiveness and low skin irritation properties has proven even more difficult. Thus, there exists a need for improved skin disinfecting formulations suitable for surgery containing PCMX.
The present invention provides an antimicrobial composition useful for preparing and disinfecting skin prior to surgery. In particular, the composition of the invention can be used as a surgical scrub formulation or pre-surgical skin disinfecting formulation. The pre-operative antimicrobial skin composition comprises parachlorometaxylenol (PCMX) as the antimicrobial agent and an anionic surfactant composition comprising a surfactant having a hydrophobic portion consisting of a linear alkyl and a hydrophilic portion having ethoxylation termination with a sulfonate anionic group; and a sarcosine surfactant. Preferably, the anionic surfactant composition further comprises a foaming anionic surfactant, such as sodium lauryl sulfate. It has now been found that antimicrobial compositions containing PCMX and a combination of certain types of anionic surfactants exhibit both a high degree of initial and persistent antimicrobial efficacy, as well as a low degree of skin irritability.
There is further disclosed an antimicrobial composition for disinfection of a skin surface consisting essentially of:
a) parachlorometaxylenol in an amount of about 3.3% by weight;
b) sodium C12-15 pareth-15 sulfonate in an amount of about 6.3% by weight;
c) sodium lauroyl sarcosinate in an amount of about 3.0% by weight;
d) sodium lauryl sulfate in an amount of about 1.05% by weight;
e) soy acid in an amount of about 0.3% by weight;
f) propylene glycol in an amount of about 9.0% by weight;
g) PEG-120 methyl glucose dioleate in an amount of about 3.0% by weight;
h) water in an amount of about 72.47% by weight;
i) phenoxyethanol in an amount of about 1.0% by weight;
j) citric acid in an amount of about 0.26% by weight;
k) sodium hydroxide in an amount of about 0.02% by weight; and
l) styrene/PVP co-polymer in an amount of about 0.3% by weight.
The invention also relates to a topical application device containing the antimicrobial composition according to the invention.
The invention further provides for a method of disinfecting skin comprising applying to the surface of the skin to be disinfected an antiseptically effective amount of an antimicrobial composition comprising parachlorometaxylenol; and an anionic surfactant composition comprising a surfactant having a hydrophobic portion consisting of a linear alkyl and a hydrophilic portion having ethoxylation termination with a sulfonate anionic group; and a sarcosine surfactant.
Among the advantages associated with the antimicrobial composition of the invention is that it exhibits the high antimicrobial effectiveness associated with PCMX while also having significantly reduced skin irritability. Another advantage of the invention is that the composition has been formulated to provide a viscous, mild and low odor product without impairing the antimicrobial efficacy of the active ingredient and cleansing properties of the surfactants used in the composition.
The antimicrobial composition of the invention comprises a combination of parachlorometaxylenol (PCMX) and additional ingredients including surfactants which when utilized provides the high degree of antiseptic efficacy of PCMX in combination with a low degree of irritation to the skin.
The antimicrobial agent, parachlorometaxylenol, is present in the composition in an antimicrobially effective amount. PCMX can be present in an amount ranging from about 1.0% to about 5.0% by weight. Preferably, PCMX is present in the composition in an amount from about 3.0% to about 4.0% by weight. In one embodiment, PCMX is present in an amount of about 3.3% by weight of the composition. A representative PCMX that can be used in the invention includes NIPACIDE(trademark) PX-R, which is available from Nipa Hardwicke, Inc. of Wilmington, Del.
The composition further comprises a combination of anionic surfactants which function to preserve the antimicrobial activity of PCMX, are compatible with the other surfactants used, and reduce the irritability of the composition. The anionic surfactant composition can collectively comprise between about 5% to about 15% by weight of the composition and includes an anionic surfactant having a hydrophobic portion consisting of a linear alkyl chain and a hydrophilic portion having ethoxylation termination and an sulfonate anionic group; and a sarcosine surfactant. In a preferred embodiment, the anionic surfactant composition further comprises a foaming anionic surfactant, such as sodium lauryl sulfate. The amounts of each surfactant in the surfactant composition can vary slightly, provided the properties contributed by each of the surfactants is maintained in the composition.
A preferred anionic sulfonate surfactant having a hydrophobic portion consisting of a linear alkyl chain and a hydrophilic portion having ethoxylation termination with an anionic sulfonate group is one having a hydrophilic portion consisting of 15 moles of ethoxylation termination and having a hydrophilic lipophilic balance (HLB) of about 15.4. Ethoxylation termination, i.e., the presence of ethoxy moieties as an end functional group on the hydrophilic portion of the compound, enhances the hydrophilic properties of the surfactant. Most preferred as the anionic sulfonate surfactant is sodium C12-15 pareth-1 5 sulfonate, which has the chemical formula H(CH2)12-15xe2x80x94(OC2H4)15xe2x80x94SO3xe2x88x92Na+(commercially available as AVANEL(trademark)S-150 from BASF Corporation, Mount Olive, N.J.). Sodium C12-15 pareth-15 sulfonate possesses a unique chemical structure and pH stability, mildness and anti-irritant properties, as well as an ability to reduce the irritability of other surfactants including sodium lauryl sulfate.
The anionic surfactant composition used in the invention also comprises a surfactant which is compatible with phenolic antimicrobial compounds. Preferred phenolic-compatible surfactants include sarcosine surfactants selected from the group comprising sodium lauroyl sarcosinate, sodium cocoyl sarcosinate, and combinations thereof. It has been found that the sarcosine surfactants are compatible with both other anionic surfactants and phenolic compounds (e.g., PCMX). Most preferred as the sarcosine surfactant is sodium lauroyl sarcosinate (commercially available as HAMPOSYL(trademark) L-30 from W. R. Grace and Co., Nashua, N.H.).
Preferably, the anionic surfactant composition further comprises a foaming anionic surfactant. Suitable foaming anionic surfactants include, but are not limited to, alkyl sulfates and alpha-olefin sulfonates, and combinations thereof. Suitable alkyl sulfates include sodium lauryl sulfate (STEPANOL(trademark) WA-EXTRA available from Stepan Company, Northfield, Ill.) and ammonium lauryl sulfate. Suitable alpha-olefin sulfonates include C14-16 olefin sulfonate. Anionic surfactants such as sodium lauryl sulfate exhibit high foaming and lather properties and provide a creamy texture to the overall composition.
The particular combination of PCMX and surfactants in the invention is important to produce the combined properties of antimicrobial efficacy and low irritability of the composition while maintaining chemical compatibility and/or stability between all the ingredients. The composition of the invention not only contains a combination of surfactants compatible with PCMX, but each surfactant is compatible with the others and enhance their respective irritation-reducing functions.
The solvent system used in the antimicrobial composition of the invention must be compatible with the ingredients of the composition. Solvents which can be used include water (deionized) and at least one solvent adapted to solubilize phenolic compounds. Solvents adapted to solubilize phenolic compounds such as PCMX include aliphatic alcohols. Suitable aliphatic alcohol solvents include, but are not limited to, propylene glycol, hexylene glycol, and triethylene glycol.
The composition can also include a pH buffer system. Any pH buffer system which is compatible with the composition ingredients and can stabilize the pH of the composition can be used. Typical pH buffer systems contain an acidulent and an alkalizing agent. Suitable acidulents include, but are not limited to, citric acid, hydrochloric acid, and phosphoric acid. Suitable alkalizing agents include, but are not limited to, sodium hydroxide (e.g., sodium hydroxide NF), and disodium phosphate.
Preferred antimicrobial compositions of the invention further comprise an emollient. Suitable emollients for the invention include, but are not limited to, vegetable fatty acids. Preferred vegetable fatty acids for use in the invention are those with phospholipids containing linoleic acid. For example, soya fatty acid can be used, such as EMERY(trademark) 610 Soya Fatty Acid available from Emery Industries, Inc./Cognis Corporation, Cincinnati, Ohio.
Viscosity enhancers or thickeners can also be included in the composition of the invention, provided they are compatible with the ingredients of the composition. Viscosity enhancers which also function as anti-irritants are preferred. Suitable thickeners include, but are not limited to, polyethylene glycol and polyethylene glycol derivatives. Polyethylene glycol derivatives which can be used include methyl glucoside derivatives, such as PEG-120 methyl glucose dioleate (commercially available as GLUCAMATE(trademark) DOE-120 from Amerchol Corporation, Edison, N.J.), PEG-120 Methyl Glucose Trioleate, PEG-150 distearate, PEG-5M and PEG-14M.
The composition of the invention can further contain other ingredients including, but not limited to, preservatives, opacifiers, foaming agents, emulsifiers, solubilizers, and the like. Preservatives which can be used include those which are typically used in topical cosmetic formulations. For example, phenoxyethanol (e.g., PHENOXYTOL(trademark) Nipa Hardwicke, Inc., Wilmington, Del.) can be used.
When opacifiers are used, any conventional opacifier adapted to remain in solution and render the composition non-transparent can be used. Suitable opacifiers include polymeric opacifiers such as styrene/polyvinylpyrrolidone co-polymers and styrene/acrylic emulsions. Styrene/polyvinylpyrrolidone co-polymers which can be used include, for example, POLECTRON(trademark) 430 (available from ISP Technologies, Inc., Calvert City, Ky.) can be used. Styrene/acrylic emulsions which can be used include sodium styrene/acrylate/divinyl-benzene co-polymer and ammonium nonoxynol-4 sulfate; sodium stytene/PEG-10 maleate/nonoxynol-10 maleate/acrylates co-polymer and ammonium nonoxynol-4 sulfate; styrene/acrylamide co-polymer and ammonium nonoxynol-4 sulfate; styrene/acrylates co-polymer and sodium lauryl sulfate and octoxynol-9; sodium styrene/acrylates co-polymer and sodium lauryl sulfate and tridecath-7; sodium methacrylate/styrene co-polymer and sodium lauryl sulfate and tridecath-7 and sodium lauryl diphenyloxide-disulfonate; and sodium styrene/acrylates co-polymer (available from CSA, Inc., Greenville, S.C.).
Variations in the type and amount of additional ingredients are possible provided that the combination thereof does not adversely affect the antimicrobial efficacy and anti-irritation properties of the overall composition.
The process for preparing the antimicrobial composition of the invention generally involves the addition of the ingredients under continuous agitation and under controlled temperature conditions. For example, the preparation of the composition can begin with the combining of PCMX, surfactants, emollient, phenol-compatible solvent (e.g., propylene glycol), and thickener while continuously stirring and warming to a temperature of about 60xc2x0 C. until the ingredients are dissolved. The temperature can then be cooled to about 45xc2x0 C. or less. The preservative (e.g., phenoxyethanol) can then be added at this time. Water can then be added as the solvent, followed by the acidulent and alkalizing agents of the pH buffer system, all while maintaining a temperature of about 45xc2x0 C. or less. Variations in the preparation process are possible.
In general, the antimicrobial composition of the invention is applied topically to the skin in the area on which the antimicrobial treatment is desired during an antiseptic cleansing procedure. The composition can be applied to the skin surface using any suitable device or technique adapted for topical delivery of liquid formulations. In a further embodiment, the antimicrobial composition of the invention can be incorporated into a topical application device. Suitable topical application devices include, but are not limited to, sponges, sponge sticks, scrub brushes, swabs, fluid dispensing devices, and the like.
The antimicrobial composition of the invention exhibits a high degree of both initial and sustained antimicrobial efficacy while at the same time exhibits a reduced degree of skin irritability normally associated with the topical use of compositions containing PCMX as the active antimicrobial agent.